The inhibitory neurotransmitter GABA has a central role in control and tuning of excitatory neuronal activity. GABA can be detected non-invasively using 1H magnetic resonance spectroscopy (MRS). We have recently shown that individuals with more GABA in occipital cortex tend to give smaller responses to visual stimuli as measured by functional magnetic resonance imaging (fMRI), suggesting that individual differences between healthy subjects may be a useful tool to investigate the mechanisms underlying the fMRI response. Understanding the relationship between the metabolic demands of excitatory and inhibitory neuronal activity and the activation recorded by fMRI is an important task in neuroscience. The overall goal of this R21 application is to investigate whether GABA concentration correlates with fMRI activation amplitude across the whole brain. This will be addressed by progressing from task activation fMRI to resting-state fMRI and from multiple single-voxel MRS measurements to spectroscopic imaging (MRSI) of GABA. PUBLIC HEALTH RELEVANCE: Functional magnetic resonance imaging (fMRI) is a very powerful method that is used by scientists to see which areas of the brain are used to perform different tasks, and to look for functional differences between the brains of healthy subjects and patients. GABA is a neurotransmitter, a chemical that is used for signaling in the brain, which is used by inhibitory neurons. This project will investigate how the size of fMRI signals is related to the concentration of GABA in different regions of the brain.